Household Transmission Dynamics of Asymptomatic SARS-CoV-2-Infected Children: A Multinational, Controlled Case-Ascertained Prospective Study.

BACKGROUND: Asymptomatic SARS-CoV-2 infection in children is highly prevalent but its acute and chronic implications have been minimally described. METHODS: In this controlled case-ascertained household transmission study, we recruited asymptomatic children <18 years with SARS-CoV-2 nucleic acid testing performed at 12 tertiary care pediatric institutions in Canada and the United States. We attempted to recruit all test-positive children and 1 to 3 test-negative, site-matched controls. After 14 days' follow-up we assessed the clinical (ie, symptomatic) and combined (ie, test-positive, or symptomatic) secondary attack rates (SARs) among household contacts. Additionally, post-COVID-19 condition (PCC) was assessed in SARS-CoV-2-positive participating children after 90 days' follow-up. RESULTS: A total of 111 test-positive and 256 SARS-CoV-2 test-negative asymptomatic children were enrolled between January 2021 and April 2022. After 14 days, excluding households with co-primary cases, the clinical SAR among household contacts of SARS-CoV-2-positive and -negative index children was 10.6% (19/179; 95% CI: 6.5%-16.1%) and 2.0% (13/663; 95% CI: 1.0%-3.3%), respectively (relative risk = 5.4; 95% CI: 2.7-10.7). In households with a SARS-CoV-2-positive index child, age <5 years, being pre-symptomatic (ie, developed symptoms after test), and testing positive during Omicron and Delta circulation periods (vs earlier) were associated with increased clinical and combined SARs among household contacts. Among 77 asymptomatic SARS-CoV-2-infected children with 90-day follow-up, 6 (7.8%; 95% CI: 2.9%-16.2%) reported PCC. CONCLUSIONS: Asymptomatic SARS-CoV-2-infected children, especially those <5 years, are important contributors to household transmission, with 1 in 10 exposed household contacts developing symptomatic illness within 14 days. Asymptomatic SARS-CoV-2-infected children may develop PCC.

Survival Benefit Associated With Participation in Clinical Trials of Anticancer Drugs: A Systematic Review and Meta-Analysis.

Importance: Many cancer clinical investigators view clinical trials as offering better care for patients than routine clinical care. However, definitive evidence of clinical benefit from trial participation (hereafter referred to as the participation effect) has yet to emerge. Objective: To conduct a systematic review and meta-analysis of the evidence examining whether patient participation in cancer trials was associated with greater survival benefit compared with routine care. Data Sources: Studies were found through PubMed and Embase (January 1, 2000, until August 31, 2022), as well as backward and forward citation searching. Study Selection: Studies were included that compared overall survival of trial participants and routine care patients. Data Extraction and Synthesis: Data extraction and methodological quality assessment were completed by 2 independent coders using Covidence software. Data were pooled using a random-effects model and analyzed based on the quality of the comparison between trial participants and routine care patients (ie, extent to which studies controlled for bias and confounders). Main Outcomes and Measures: The hazard ratio (HR) for overall survival of trial participants vs routine care patients. Results: Thirty-nine publications were included, comprising 85 comparisons of trial participants and routine care patients. The meta-analysis revealed a statistically significant overall survival benefit for trial participants (HR, 0.76 [95% CI, 0.69-0.82]) when all studies were pooled, regardless of design or quality. However, survival benefits diminished in study subsets that matched trial participants and routine care patients for eligibility criteria (HR, 0.85 [95% CI, 0.75-0.97]) and disappeared when only high-quality studies were pooled (HR, 0.91 [95% CI, 0.80-1.05]). They also disappeared when estimates were adjusted for potential publication bias (HR, 0.94 [95% CI, 0.86-1.03]). Conclusions and Relevance: Many studies suggest a survival benefit for cancer trial participants. However, these benefits were not detected in studies using designs addressing important sources of bias and confounding. Pooled results of high-quality studies are not consistent with a beneficial effect of trial participation on its own.

Effectiveness of Coronavirus Disease 2019 Vaccines Against Hospitalization and Death in Canada: A Multiprovincial, Test-Negative Design Study.

BACKGROUND: A major goal of coronavirus disease 2019 (COVID-19) vaccination is to prevent severe outcomes (hospitalizations and deaths). We estimated the effectiveness of messenger RNA (mRNA) and ChAdOx1 COVID-19 vaccines against severe outcomes in 4 Canadian provinces between December 2020 and September 2021. METHODS: We conducted this multiprovincial, retrospective, test-negative study among community-dwelling adults aged ≥18 years in Ontario, Quebec, British Columbia, and Manitoba using linked provincial databases and a common study protocol. Multivariable logistic regression was used to estimate province-specific vaccine effectiveness against COVID-19 hospitalization and/or death. Estimates were pooled using random-effects models. RESULTS: We included 2 508 296 tested participants, with 31 776 COVID-19 hospitalizations and 5842 deaths. Vaccine effectiveness was 83% after a first dose and 98% after a second dose against both hospitalization and death (separately). Against severe outcomes, effectiveness was 87% (95% confidence interval [CI], 71%-94%) ≥84 days after a first dose of mRNA vaccine, increasing to 98% (95% CI, 96%-99%) ≥112 days after a second dose. Vaccine effectiveness against severe outcomes for ChAdOx1 was 88% (95% CI, 75%-94%) ≥56 days after a first dose, increasing to 97% (95% CI, 91%-99%) ≥56 days after a second dose. Lower 1-dose effectiveness was observed for adults aged ≥80 years and those with comorbidities, but effectiveness became comparable after a second dose. Two doses of vaccines provided very high protection for both homologous and heterologous schedules and against Alpha, Gamma, and Delta variants. CONCLUSIONS: Two doses of mRNA or ChAdOx1 vaccine provide excellent protection against severe outcomes.

What explains racial/ethnic inequities in the uptake of differentiated influenza vaccines?

We investigated the role of individual, community and vaccinator characteristics in mediating racial/ethnic disparities in the uptake of differentiated influenza vaccines (DIVs; including high-dose, adjuvanted, recombinant and cell-based vaccines). We included privately-insured (commercial and Medicare Advantage) ≥65 years-old community-dwelling health plan beneficiaries in the US with >1 year of continuous coverage and who received ≥1 influenza vaccine during the study period (July 2014-June 2018). Of 2.8 million distinct vaccination claims, 60% were for DIVs; lower if received in physician offices (49%) compared to pharmacies/facilities (74%). Among those vaccinated in physician offices, non-whites had lower odds of receiving a DIV if they lived in a non-minority county (0.77;95%CI 0.75-0.80) and even lower odds if they lived in a minority county (0.62;0.60-0.63). Differences in education, household income, medical history, community and vaccinator characteristics did not fully explain the disparities. Similar patterns emerged for vaccinations in pharmacies/facilities, although disparities disappeared altogether after controlling for socio-economic and vaccinator characteristics. When vaccinated in physician offices, minority county residents were less likely to receive a DIV, especially for non-whites (0.72;0.67-0.78). These disparities disappeared for whites, but not for non-whites, after controlling for community and vaccinator characteristics. We found an alarming level of inequity in DIV vaccine uptake among fully insured older adults that could not be fully explained by differences in sociodemographic, medical, community, and vaccinator characteristics. New strategies are urgently needed to address these inequities.

A Call for Caution in Use of Pertussis Vaccine Effectiveness Studies to Estimate Waning Immunity: A Canadian Immunization Research Network Study.

BACKGROUND: Vaccine effectiveness (VE) studies provide essential evidence on waning vaccine-derived immunity, a major threat to pertussis control. We evaluated how study design affects estimates by comparing 2 case-control studies conducted in Ontario, Canada. METHODS: We compared results from a test-negative design (TND) with a frequency-matched design (FMD) case-control study using pertussis cases from 2005-2015. In the first study, we identified test-negative controls from the public health laboratory that diagnosed cases and, in the second, randomly selected controls from patients attending the same physicians that reported cases, frequency matched on age and year. We compared characteristics of cases and controls using standardized differences. RESULTS: In both designs, VE estimates for the early years postimmunization were consistent with clinical trials (TND, 84%; FMD, 89% at 1-3 years postvaccination) but diverged as time since last vaccination increased (TND, 41%; FMD, 74% by 8 years postvaccination). Overall, we observed lower VE and faster waning in the TND than the FMD. In the TND but not FMD, controls differed from cases in important confounders, being younger, having more comorbidities, and higher healthcare use. Differences between the controls of each design were greater than differences between cases. TND controls were more likely to be unvaccinated or incompletely vaccinated than FMD controls (P < .001). CONCLUSIONS: The FMD adjusted better for healthcare-seeking behavior than the TND. Duration of protection from pertussis vaccines is unclear because estimates vary by study design. Caution should be exercised by experts, researchers, and decision makers when evaluating evidence on optimal timing of boosters.

Sociodemographic and health-related determinants of seasonal influenza vaccination in pregnancy: A systematic review and meta-analysis of the evidence since 2000.

INTRODUCTION: Vaccination is considered to be the most practical and effective preventative measure against influenza. It is highly recommended for population subgroups most at risk of developing complications, including pregnant women. However, seasonal influenza vaccine uptake remains suboptimal among pregnant women, even in jurisdictions with universal vaccination. We summarized the evidence on the determinants of seasonal influenza vaccine uptake during pregnancy to better understand factors that influence vaccine uptake among pregnant women. MATERIAL AND METHODS: We systematically searched MEDLINE, Embase and CINAHL from January 2000 to February 2020 for publications in English reporting on sociodemographic and/or health-related determinants of seasonal influenza vaccine uptake during pregnancy. Two reviewers independently included studies. One reviewer extracted data and assessed study quality, and another reviewer checked extracted data and study quality assessments for errors. Disagreements were resolved through consensus, or a third reviewer. We meta-analyzed using the inverse variance, random-effects method, and reported the odds ratios (OR) and 95% confidence intervals (CI). RESULTS: From 1663 retrieved citations, we included 36 studies. The following factors were associated with increased seasonal influenza vaccine uptake: Older age (20 studies: OR 1.13, 95% CI 1.07-1.20), being nulliparous (13 studies: OR 1.26, 95% CI 1.15-1.38), married (8 studies: OR 1.11, 95% CI 1.07-1.15), employed (4 studies: OR 1.13, 95% CI 1.02-1.24), a non-smoker (8 studies: OR 1.25, 95% CI 1.04-1.51) and having prenatal care (3 studies: OR 3.36, 95% CI 2.25-5.02), a chronic condition (6 studies: OR 1.30, 95% CI 1.17-1.44), been previously vaccinated (9 studies: OR 4.88, 95% CI 3.14-7.57) and living in a rural area (9 studies: OR 1.09, 95% CI 1.05-1.14). Compared with being black, being white was also associated with increased seasonal influenza vaccine uptake (11 studies: OR 1.30, 95% CI 1.20-1.41). CONCLUSIONS: The evidence suggests that several sociodemographic and health-related factors may determine seasonal influenza vaccination in pregnancy, and that parity, history of influenza vaccination, prenatal care and comorbidity status may be influential.

Interventions on health care providers to improve seasonal influenza vaccination rates among patients: a systematic review and meta-analysis of the evidence since 2000.

BACKGROUND: Seasonal influenza vaccination (SIV) rates remain suboptimal in many populations, even in those with universal SIV. OBJECTIVE: To summarize the evidence on interventions on health care providers (physicians/nurses/pharmacists) to increase SIV rates. METHODS: We systematically searched/selected full-text English publications from January 2000 to July 2019 (PROSPERO-CRD42019147199). Our outcome was the difference in SIV rates between patients in intervention and non-intervention groups. We calculated pooled difference using an inverse variance, random-effects model. RESULTS: We included 39 studies from 8370 retrieved citations. Compared with no intervention, team-based training/education of physicians significantly increased SIV rates in adult patients: 20.1% [7.5-32.7%; I2 = 0%; two randomized controlled trials (RCTs)] and 13.4% [8.6-18.1%; I2 = 0%; two non-randomized intervention studies (NRS)]. A smaller increase was observed in paediatric patients: 7% (0.1-14%; I2 = 0%; two NRS), and in adult patients with team-based training/education of physicians and nurses together: 0.9% (0.2-1.5%; I2 = 30.6%; four NRS). One-off provision of guidelines/information to physicians, and to both physicians and nurses, increased SIV rates in adult patients: 23.8% (15.7-31.8%; I2 = 45.8%; three NRS) and paediatric patients: 24% (8.1-39.9%; I2 = 0%; two NRS), respectively. Use of reminders (prompts) by physicians and nurses slightly increased SIV rates in paediatric patients: 2.3% (0.5-4.2%; I2 = 0%; two RCTs). A larger increase was observed in adult patients: 18.5% (14.8-22.1%; I2 = 0%; two NRS). Evidence from both RCTs and NRS showed significant increases in SIV rates with varied combinations of interventions. CONCLUSIONS: Limited evidence suggests various forms of physicians' and nurses' education and use of reminders may be effective for increasing SIV rates among patients.

Assessing the prior event rate ratio method via probabilistic bias analysis on a Bayesian network.

BACKGROUND: Unmeasured confounders are commonplace in observational studies conducted using real-world data. Prior event rate ratio (PERR) adjustment is a technique shown to perform well in addressing such confounding. However, it has been demonstrated that, in some circumstances, the PERR method actually increases rather than decreases bias. In this work, we seek to better understand the robustness of PERR adjustment. METHODS: We begin with a Bayesian network representation of a generalized observational study, which is subject to unmeasured confounding. Previous work evaluating PERR performance used Monte Carlo simulation to calculate joint probabilities of interest within the study population. Here, we instead use a Bayesian networks framework. RESULTS: Using this streamlined analytic approach, we are able to conduct probabilistic bias analysis (PBA) using large numbers of combinations of parameters and thus obtain a comprehensive picture of PERR performance. We apply our methodology to a recent study that used the PERR in evaluating elderly-specific high-dose (HD) influenza vaccine in the US Veterans Affairs population. That study obtained an HD relative effectiveness of 25% (95% CI: 2%-43%) against influenza- and pneumonia-associated hospitalization, relative to standard-dose influenza vaccine. In this instance, we find that the PERR-adjusted result is more like to underestimate rather than to overestimate the relative effectiveness of the intervention. CONCLUSIONS: Although the PERR is a powerful tool for mitigating the effects of unmeasured confounders, it is not infallible. Here, we develop some general guidance for when a PERR approach is appropriate and when PBA is a safer option.

Prenatal antibiotic exposure and risk of attention-deficit/hyperactivity disorder: a population-based cohort study.

BACKGROUND: Abnormal microbiota composition induced by prenatal exposure to antibiotics has been proposed as a potential contributor to the development of attention-deficit/hyperactivity disorder (ADHD). We examined the association between prenatal antibiotic exposure and risk of ADHD. METHODS: We conducted a population-based retrospective cohort study of children born in Manitoba, Canada, between 1998 and 2017 and their mothers. We defined exposure as the mother having filled 1 or more antibiotic prescriptions during pregnancy. The outcome was diagnosis of ADHD in the offspring, as identified in administrative databases. We estimated hazard ratios (HRs) using Cox proportional hazards regression in the overall cohort, in a separate cohort matched on high-dimensional propensity scores and in a sibling cohort. RESULTS: In the overall cohort, consisting of 187 605 children, prenatal antibiotic dispensation was associated with increased risk of ADHD (HR 1.22, 95% confidence interval [CI] 1.18-1.26). Similar results were observed in the matched cohort of 129 674 children (HR 1.20, 95% CI 1.15-1.24) but not in the sibling cohort (HR 1.06, 95% CI 0.99-1.13). Two negative-control analyses indicated a positive association with ADHD despite the lack of a reasonable biological mechanism, which suggested that the observed association between prenatal antibiotic dispensation and risk of ADHD was likely due to confounding. INTERPRETATION: In our study, prenatal antibiotic exposure was not associated with increased risk of ADHD in children. Although the risk was higher in the overall and matched cohorts, it was likely overestimated because of unmeasured confounding. Future studies are warranted to examine other factors affecting microbiota composition in association with risk of ADHD.

High-dose influenza vaccination and mortality among predominantly male, white, senior veterans, United States, 2012/13 to 2014/15.

IntroductionIt is unclear whether high-dose influenza vaccine (HD) is more effective at reducing mortality among seniors.AimThis study aimed to evaluate the relative vaccine effectiveness (rVE) of HD. MethodsWe linked electronic medical record databases in the Veterans Health Administration (VHA) and Medicare administrative files to examine the rVE of HD vs standard-dose influenza vaccines (SD) in preventing influenza/pneumonia-associated and cardiorespiratory mortality among VHA-enrolled veterans 65 years or older during the 2012/13, 2013/14 and 2014/15 influenza seasons. A multivariable Cox proportional hazards model was performed on matched recipients of HD vs SD, based on vaccination time, location, age, sex, ethnicity and VHA priority level. ResultsAmong 569,552 person-seasons of observation, 207,574 (36%) were HD recipients and 361,978 (64%) were SD recipients, predominantly male (99%) and white (82%). Pooling findings from all three seasons, the adjusted rVE estimate of HD vs SD during the high influenza periods was 42% (95% confidence interval (CI): 24-59) against influenza/pneumonia-associated mortality and 27% (95% CI: 23-32) against cardiorespiratory mortality. Residual confounding was evident in both early and late influenza periods despite matching and multivariable adjustment. Excluding individuals with high 1-year predicted mortality at baseline reduced the residual confounding and yielded rVE of 36% (95% CI: 10-62) and 25% (95% CI: 12-38) against influenza/pneumonia-associated and cardiorespiratory mortality, respectively. These were confirmed by results from two-stage residual inclusion estimations.DiscussionThe HD was associated with a lower risk of influenza/pneumonia-associated and cardiorespiratory death in men during the high influenza period.

Effectiveness of school-based and high-risk human papillomavirus vaccination programs against cervical dysplasia in Manitoba, Canada.

The effectiveness of a vaccination program is influenced by its design and implementation details and by the target population characteristics. Using routinely collected population-based individual-level data, we assessed the effectiveness (against cervical dysplasia) of Manitoba's quadrivalent human papillomavirus (qHPV) routine school-based vaccination program and a short-lived campaign that targeted women at high-risk of developing cervical cancer. Females ≥9 years old who received the qHPV vaccine in Manitoba (Canada) between September 1, 2006, and March 31, 2013 (N = 31,442) were matched on age and area of residence to up to three unvaccinated females. Cox proportional hazards models were used to estimate qHPV VE against high-grade (HSILs) and low-grade squamous intraepithelial lesions (LSILs) and atypical squamous cells of undetermined significance (ASCUS). Among 14-17-year-old participants who had Pap cytology after enrollment, the adjusted qHPV VE estimates were 30% (17-58%) and 36% (21-48%) against the detection of HSILs and LSILs, respectively. There was, however, no evidence of program effectiveness among females vaccinated at ≥18 years of age and among those with a history of abnormal cytology, who were mostly vaccinated as part of the high-risk program. Estimates of VE for females vaccinated in the school-based program are consistent with the expected benefits from qHPV vaccination. No similar benefits were detected among women vaccinated at an older age, and those with abnormal cytology, who were targeted by the high-risk program. Further efforts should be targeted at achieving higher vaccine coverage among preadolescents, prior to the initiation of sexual activity.

Antibiotic Exposure in the First Year of Life and the Risk of Attention-Deficit/Hyperactivity Disorder: A Population-Based Cohort Study.

Early childhood antibiotic exposure induces changes in gut microbiota reportedly associated with the development of attention-deficit/hyperactivity disorder (ADHD). We conducted a population-based cohort study to examine the association between antibiotic use in the first year of life and ADHD risk. We included children born in Manitoba, Canada, between 1998 and 2017. Exposure was defined as having filled 1 or more antibiotic prescriptions during the first year of life. ADHD diagnosis was identified in hospital abstracts, physician visits, or drug dispensations. Risk of developing ADHD was estimated using Cox proportional hazards regression in a high-dimensional propensity score-matched cohort (n = 69,738) and a sibling cohort (n = 67,671). ADHD risk was not associated with antibiotic exposure in the matched-cohort (hazard ratio = 1.02, 95% confidence interval: 0.97, 1.08) or in the sibling cohort (hazard ratio = 0.96, 95% confidence interval: 0.89, 1.03). In secondary analyses of the matched cohort, ADHD risk increase was observed in those exposed to 4 or more antibiotic courses or a duration longer than 3 weeks. These associations were not observed in the sibling cohort. We concluded that antibiotic exposure in the first year of life does not pose an ADHD risk on a population level.

Relative Vaccine Effectiveness of High-Dose Versus Standard-Dose Influenza Vaccines Among Veterans Health Administration Patients.

Background: We examined whether a high-dose inactivated influenza vaccine was more efficacious in preventing hospitalizations than a standard-dose vaccine in the Veterans Health Administration (VHA) senior population. Methods: This study estimated the relative vaccine effectiveness (rVE) of high dose versus standard dose using a retrospective cohort of VHA patients 65 years of age or older in the 2015-2016 influenza season. To adjust for measured confounders, we matched each high-dose recipient with up to 4 standard-dose recipients vaccinated at the same location within a 2-week period and having 2 or more pre-existing medical comorbidities. We used the previous event rate ratio method (PERR), a type of difference-in-differences analysis, to adjust for unmeasured confounders. Results: We evaluated 104965 standard-dose and 125776 high-dose recipients; matching decreased the population to 49091 standard-dose and 24682 high-dose recipients. The matched, PERR-adjusted rVE was 25% (95% confidence interval [CI], 2%-43%) against influenza- or pneumonia-associated hospitalization, 7% (95% CI, -2% to 14%) against all-cause hospitalization, 14% (95% CI, -8% to 32%) against influenza- or pneumonia-associated outpatient visit, 5% (95% CI, 2%-8%) against all-cause outpatient visit, and 38% (95% CI, -5% to 65%) against laboratory-confirmed influenza. Conclusions: In protecting senior VHA patients against influenza- or pneumonia-associated hospitalization, a high-dose influenza vaccine is more effective than a standard-dose vaccine.

Registry Cohort Study to Determine Risk for Multiple Sclerosis after Vaccination for Pandemic Influenza A(H1N1) with Arepanrix, Manitoba, Canada.

To investigate a potential risk for multiple sclerosis (MS) after vaccination with Arepanrix, the GlaxoSmithKline AS03-adjuvanted influenza A(H1N1)pdm09 vaccine, we used the provincewide immunization registry for Manitoba, Canada, to match 341,347 persons vaccinated during the 2009 pandemic to 485,941 unvaccinated persons on age, sex, address, and a propensity score measuring the probability of vaccination. We used a previously validated algorithm to identify MS cases from provincial hospital, physician, and prescription drug claims databases. After 12 months of follow-up, the age-adjusted incidence rate of MS was 17.7 cases per 100,000 person-years in the Arepanrix cohort and 24.2 per 100,000 in the unvaccinated cohort. The corresponding adjusted hazard ratio was 0.9. We observed similar patterns when we measured incidence over the entire follow-up period. The AS03 adjuvant, a candidate for inclusion in future pandemic vaccines, does not appear to increase the short-term risk for MS when included in influenza vaccines.

Associations between statin use and risk of non-Hodgkin lymphomas by subtype.

Non-Hodgkin lymphomas (NHL) are a group of cancers with highly heterogeneous biology and clinical features. Statins are increasingly prescribed to prevent cardiovascular diseases. Early evidence shows a preventive effect of statins for some cancers, but their effect on NHL risk is unclear. We conducted a population-based nested case-control study involving 5,541 NHL cases and 27,315 controls matched for gender, age, place of residence and length of period of available prescription drug data. We assessed the use of statins prior to diagnosis (excluding the 12 months prior to the index date). We used conditional logistic regression models to estimate odds ratio (OR) and 95% confidence interval (CI) for use of any statin, adjusting for medical conditions, number of family physician visits for 5 years prior to index date, healthcare utilization, income and use of other medications. Over one-quarter of cases and controls were prescribed statins. Ever-use of any statin was associated with lower risk of Total NHL (OR = 0.82, 95% CI 0.76-0.89) and of certain subtypes including diffuse large B-cell lymphomas (DLBCL, OR = 0.77, 95% CI 0.65-0.92), plasma cell neoplasms (PCN, OR = 0.76, 95% CI 0.63-0.91) and other B-cell NHL (0.75, 0.59-0.95). Analysis by statin type suggested that the association was limited to high potency statin and lipophilic statin users. No clear duration or dose-response relationships were observed. Our findings provide evidence that statin use can reduce the risk of DLBCL and plasma cell lymphomas, but not other NHL types. Further studies are warranted to verify these associations and to examine the biological mechanisms.

The effect of statin use on the incidence of prostate cancer: A population-based nested case-control study.

Preclinical studies suggest statins may help prevent prostate cancer (PC), but epidemiologic results are mixed. Many epidemiological studies have relatively short prediagnosis drug exposure data, which may miss some statin use. We completed a nested case-control study investigating the impact of statin use on PC diagnosis and clinically significant PC using data from men aged ≥40 years in the Canadian province of Saskatchewan between 1990 and 2010. Drug exposure histories were derived from a population-based prescription drug database. We used conditional logistic regression to model use of statins as a class and stratified analyses for groups defined by lipophilicity. Clinically significant PC was defined as Gleason score 8-10 OR stage C or D or III or IV at diagnosis. 12,745 cases of PC were risk-set matched on age and geographic location to 50,979 controls. Greater than 90% of subjects had prediagnosis drug exposure histories >15 years. 2,064 (16.2%) cases and 7,956 (15.6%) controls were dispensed one or more statin prescriptions. In multivariable models, ever prescription of statins was not associated with PC diagnosis (OR 0.97; 95% CI 0.90-1.05). Neither lipophilic statins (OR 0.96, 95% CI 0.88-1.04) nor hydrophilic statins (OR 1.06, 95% CI 0.95-1.20) impacted PC diagnosis. There was no effect of the dose or duration of statin use. Diagnosis of clinically significant PC decreased with statin use (OR 0.84, 95% CI 0.73-0.97). Statin use is not associated with overall PC risk, regardless of duration or dose of statin exposure. Statin use is associated with a decreased risk of clinically significant PC.

Prenatal antibiotic exposure and childhood asthma: a population-based study.

Antibiotic use during infancy alters gut microbiota and immune development and is associated with an increased risk of childhood asthma. The impact of prenatal antibiotic exposure is unclear. We sought to characterise the association between prenatal antibiotic exposure and childhood asthma.We performed a population-based cohort study using prescription records, hospitalisation records and physician billing claims from 213 661 mother-child dyads born in Manitoba, Canada between 1996 and 2012. Associations were determined using Cox regression, adjusting for maternal asthma, postnatal antibiotics and other potential confounders. Sensitivity analyses evaluated maternal antibiotic use before and after pregnancy.36.8% of children were exposed prenatally to antibiotics and 10.1% developed asthma. Prenatal antibiotic exposure was associated with an increased risk of asthma (adjusted hazard ratio (aHR) 1.23, 95% CI 1.20-1.27). There was an apparent dose response (aHR 1.15, 95% CI 1.11-1.18 for one course; aHR 1.26, 95% CI 1.21-1.32 for two courses; and aHR 1.51, 95% CI 1.44-1.59 for three or more courses). Maternal antibiotic use during 9 months before pregnancy (aHR 1.27, 95% CI 1.24-1.31) and 9 months postpartum (aHR 1.32, 95% CI 1.28-1.36) were similarly associated with asthma.Prenatal antibiotic exposure was associated with a dose-dependent increase in asthma risk. However, similar associations were observed for maternal antibiotic use before and after pregnancy, suggesting the association is either not directly causal, or not specific to pregnancy.

Early Evidence of the Effectiveness of the Human Papillomavirus Vaccination Program Against Anogenital Warts in Manitoba, Canada: A Registry Cohort Study.

BACKGROUND: We assessed the effectiveness of the quadrivalent human papillomavirus vaccine (qHPV) vaccination program in Manitoba, Canada, in reducing incident anogenital warts (AGWs) and to what extent effectiveness depends on age at vaccination and number of doses. METHODS: Female participants 9 years or older who received the qHPV in Manitoba between September 2006 and March 2013 (n = 31,464) through the publicly funded school-based program and a high-risk catch-up program were included. They were matched on age and area of residence to unvaccinated female participants. Information on incident AGWs was obtained from provincial administrative databases using validated algorithms. Using stratified Cox regression models, we estimate hazard ratios (HRs) for the association between qHPV and AGWs. RESULTS: For female participants vaccinated at age 18 years or younger, receipt of qHPV was associated with a 40% reduction in AGW risk (HR, 0.6; 95% confidence interval [CI], 0.4-0.8). Further adjustment for socioeconomic and medical history did not alter this estimate. For women vaccinated at age 19 years or older, we saw an increase in AGW incidence, especially among those who were sexually active (HR, 2.8; 95% CI, 2.1-3.7). Among female participants vaccinated at age 18 years or younger, risk of AGWs was lowest among those who received 3 doses, corresponding to a vaccine effectiveness of 56% (95% CI, 30%-70%). For women vaccinated at older age, risk of AGWs remained increased regardless of the number of doses. CONCLUSIONS: Women vaccinated at an older (≥19 years) age may be less protected against AGWs, particularly if sexually active before vaccine administration. Further efforts should be targeted at increasing vaccine uptake among preadolescents before the initiation of sexual activity.

Associations between statin use and non-Hodgkin lymphoma (NHL) risk and survival: a meta-analysis.

Evidence on the effect of statin use on non-Hodgkin lymphoma (NHL) is not clear. We conducted a systematic review and meta-analysis to examine the associations between statin use and NHL risk and survival. We searched multiple literature sources up to October 2014 and identified 10 studies on the risk of diagnosis with NHL and 9 studies on survival. Random effects model was used to calculate pooled odds ratio (PORs) for risk and pooled hazard ratio (PHR) for survival. Heterogeneity among studies was examined using the Tau-squared and the I-squared (I2 ) tests. Statin use was associated with reduced risk for total NHL (POR = 0.82, 95% CI 0.69-0.99). Among statin users, there was a lower incidence risk for marginal zone lymphoma (POR = 0.54, 95% CI 0.31-0.94), but this was not observed for other types of NHL. However, statin use did not affect overall survival (PHR = 1.02, 95% CI 0.99-1.06) or event-free survival (PHR = 0.99, 95% CI 0.87-1.12) in diffuse large B-cell lymphoma. There is suggestive epidemiological evidence that statins decrease the risk of NHL, but they do not influence survival in NHL patients. Copyright © 2015 John Wiley & Sons, Ltd.

Biologic and epidemiologic evidence assessing if statins prevent prostate cancer.

INTRODUCTION: During their lives, 1 in 8 men will be diagnosed with prostate cancer. Several drugs have been shown to decrease prostate cancer risk, but have not been widely used in prostate cancer prevention because of concerns about side-effects and cost-effectiveness. Statins are indicated for prevention of cardiovascular disease, have an excellent benefit to risk profile, and some studies suggest that statins may reduce the risk of prostate cancer. MATERIALS AND METHODS: We performed a systematic search of Medline (Ovid), EMBASE (Ovid), and PubMed. This search informed a narrative review of the biological rationale for why statins may reduce prostate cancer risk and an evaluation of the existing epidemiological evidence to determine whether further studies are needed to assess the true impact of statins on prostate cancer risk. RESULTS: Statins may help prevent the development of prostate cancer through inhibition of sustained proliferative signals (androgen and Ras/Rho), sensitizing potentially malignant cells to programmed cell death, minimizing inflammation, reducing angiogenesis, and impeding invasiveness by blocking adhesion molecules. The epidemiologic literature examining the effect of statin use on overall prostate cancer diagnosis is highly heterogeneous, with relative risks of 0.26 to 2.94. Out of 33 published studies, 5 show an increased risk of prostate cancer with statin use, 10 demonstrate a decreased risk, and 18 suggest no effect. CONCLUSION: There is a compelling pre-clinical rationale for statins as potential chemopreventive agents. However, large, population-based studies with long pre-diagnosis drug exposure data are needed to investigate the impact of statin exposure on prostate cancer incidence.